Several diseases of humans, such as synergistic gas gangrene and dental caries, are caused by pathogenic microbial consortia. Such pathogenic microbial communities can range from apparently unorganized and random to highly structured and functionally complex. One very complex pathogenic microbial consortium is black band disease (BBD) of corals. BBD is a unique host/pathogen association in which a cyanobacterial dominated, laminated microbial mat (i.e. thick biofilm) infects and kills coral tissue. The consortium is highly organized and structured, and the entire intact community migrates across susceptible coral colonies, completely degrading coral tissue and leaving behind bare coral skeleton. After 30 years of study, involving several teams and approaches, the identity of the pathogen, or determination of the involvement of a primary pathogen as opposed to a true pathogenic consortium, is unknown. The BBD/coral model presents an opportunity to investigate the intricacies of pathogenic microbial consortium development in a relatively simple system. The overall objective of the proposed research is to investigate the pathogenicity of BBD based on the microbial commmunity organization of the consortium. The overall goals of this research are to: 1) dissect the BBD microbial community in terms of the functional (physiological, developmental, and self-sustaining) activities of the specific microorganisms involved; 2) determine if there is a requirement of a physiologically functional, spatially structured consortium for pathogenicity; and 3) assess the host (coral) response to the disease (BBD toxicity). Research will be conducted within the following four specific aims: 1) Molecular community profiling of BBD over time (during disease development and progression)using Amplicon length heterogeneity (ALH) PCR. 2) Characterization of the consortium by identification of key microorganisms and functional microbial communities via enrichment and cultivation, molecular sequencing, and FISH. 3) Elucidation of the importance of each functional microbial community within the BBD pathogenic microbial consortium by using inhibitors of each metabolic group. 4) Identification and quantification of cyanobacterial toxins produced within BBD. Research will include a combination of physiological, biochemical, and molecular experiments. Our findings may lead to the development of new approaches to the study of human biofilm-associated microbial diseases.